Acute kidney injury (AKI) is a common complication of critical illness, with even minor degrees of AKI conferring an independent risk of death (1, 2). No therapy currently exists that has been definitively demonstrated to improve outcomes in AKI, although renal replacement therapy (RRT) is frequently necessary as a life-sustaining measure once oliguria, severe azotemia, or significant electrolyte abnormalities develop. Defining the indications for and timing of RRT in the setting of AKI is a priority research topic identified by the Acute Kidney Injury Network. Prior studies examining timing of RRT in acute kidney injury typically have been limited to patients with AKI who received RRT, rendering them unable to evaluate the indications for this therapy, and the impact of therapy versus no therapy (3, 4). Reframing the questions regarding RRT in the setting of AKI, we have designed a study to examine the impact on mortality of initiating dialysis therapy during a period of moderate metabolic disarray, defined as the period of time after acute kidney injury, when laboratory abnormalities are detectable, but before absolute indications for dialysis have arisen. We take advantage of the variations in clinical practice during early AKI prior to when RRT is required as a life-sustaining measure to design an observational study that will permit us to accomplish the following specific aims: Aim 1: Develop a metric defining moderate metabolic disarray and assess the association of duration and severity of moderate metabolic disarray prior to initiation of RRT with the rate of mortality. We will create a score based on a multiple regression model of likelihood to receive dialysis based on a variety of factors, and use that likelihood to define degree of disarray. We will then assess the impact of duration and severity of moderate disarray with these methods (censored at initiation of dialysis or development of severe disarray) on predicting in-hospital mortality. Aim 2: Assess the impact of renal replacement therapy (RRT) initiated during moderate metabolic disarray on in-hospital mortality in a cohort of critically ill patients with AKI The proposed research project will be in the context of the applicant working towards a Masters of Science in Clinical Epidemiology, whereby didactic learning in the classroom, focusing on fundamentals of epidemiology, study design, and statistical and analytic methods of research will enhance and guide the research process of the applicant. The long-term objectives of the applicant for this project are to collect and analyze the data, prepare manuscripts for publication, and build upon the data as part of a future application for a K award. PUBLIC HEALTH RELEVANCE: The proposed research herein will have a significant impact on the treatment of acute kidney injury in hospitalized patients. Currently, large variation exists in opinion on appropriate timing of initiation of dialysis after AKI. This study will provide evidence of benefit or harm from initiation of dialytic therapy during moderate metabolic disarray, advancing our understanding of the syndrome of AKI and helping us to more consistently treat patients.